title: Murine model to study the invasion and survival of Mycobacterium tuberculosis in the central nervous system.
abstract: BACKGROUND
  Tuberculosis of the central nervous system (CNS) is a serious, often fatal disease primarily affecting young children. It develops after hematogenous dissemination and subsequent invasion of the CNS by Mycobacterium tuberculosis. The microbial determinants involved in CNS disease are poorly characterized.
  
  
  METHODS
  Hematogenously disseminated M. tuberculosis infection was simulated in BALB/c mice by intravenous challenge. Bacteria were recovered using standard culture techniques. Host immune response to M. tuberculosis infection was assessed by histopathological and cytokine profile analysis. By means of a pooled infection with genotypically defined M. tuberculosis mutants, bacterial genes required for invasion or survival were determined in the CNS and lung tissue.
  
  
  RESULTS
  M. tuberculosis were detected in whole mouse brains as early as 1 day after intravenous infection and at all time points assessed thereafter. No significant immune response was elicited in the infected brain tissue, compared with extensive inflammation in the infected lung tissue at the same time point. We identified mutants for 5 M. tuberculosis genes (Rv0311, Rv0805, Rv0931c, Rv0986, and MT3280) with CNS-specific phenotypes, absent in lung tissue.
  
  
  CONCLUSIONS
  We have identified CNS-specific M. tuberculosis genes involved in the pathogenesis of tuberculosis. Further characterization of these genes will help in understanding the microbial pathogenesis of CNS tuberculosis.
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Be
authors.forename: Gyanu
authors.initials: G
authors.lastname: Lamichhane
authors.forename: Jacques
authors.initials: J
authors.lastname: Grosset
authors.forename: Sandeep
authors.initials: S
authors.lastname: Tyagi
authors.forename: Qi-Jian
authors.initials: QJ
authors.lastname: Cheng
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000382:microbiology*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000502:physiology*; D020306:Tuberculosis, Central Nervous System / Q000276:immunology / Q000382:microbiology*
chemical_list: D016207:Cytokines